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1.
PLoS Pathog ; 17(12): e1010175, 2021 12.
Article in English | MEDLINE | ID: covidwho-1592244

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Currently, as dangerous mutations emerge, there is an increased demand for specific treatments for SARS-CoV-2 infected patients. The spike glycoprotein on the virus envelope binds to the angiotensin converting enzyme 2 (ACE2) on host cells through its receptor binding domain (RBD) to mediate virus entry. Thus, blocking this interaction may inhibit viral entry and consequently stop infection. Here, we generated fusion proteins composed of the extracellular portions of ACE2 and RBD fused to the Fc portion of human IgG1 (ACE2-Ig and RBD-Ig, respectively). We demonstrate that ACE2-Ig is enzymatically active and that it can be recognized by the SARS-CoV-2 RBD, independently of its enzymatic activity. We further show that RBD-Ig efficiently inhibits in-vivo SARS-CoV-2 infection better than ACE2-Ig. Mechanistically, we show that anti-spike antibody generation, ACE2 enzymatic activity, and ACE2 surface expression were not affected by RBD-Ig. Finally, we show that RBD-Ig is more efficient than ACE2-Ig at neutralizing high virus titers. We thus propose that RBD-Ig physically blocks virus infection by binding to ACE2 and that RBD-Ig should be used for the treatment of SARS-CoV-2-infected patients.


Subject(s)
Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Immunoglobulin Fc Fragments/metabolism , Immunoglobulin G/metabolism , Protein Domains , Recombinant Fusion Proteins/metabolism , SARS-CoV-2/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Animals , Binding Sites , Binding Sites, Antibody , COVID-19/prevention & control , Chlorocebus aethiops , Female , HEK293 Cells , Humans , Immunoglobulin Fc Fragments/therapeutic use , Immunoglobulin G/therapeutic use , Mice, Transgenic , Neutralization Tests , Protein Binding , Recombinant Fusion Proteins/therapeutic use , SARS-CoV-2/drug effects , Vero Cells
2.
Commun Biol ; 4(1): 1389, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1585764

ABSTRACT

In light of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants potentially undermining humoral immunity, it is important to understand the fine specificity of the antiviral antibodies. We screened 20 COVID-19 patients for antibodies against 9 different SARS-CoV-2 proteins observing responses against the spike (S) proteins, the receptor-binding domain (RBD), and the nucleocapsid (N) protein which were of the IgG1 and IgG3 subtypes. Importantly, mutations which typically occur in the B.1.351 "South African" variant, significantly reduced the binding of anti-RBD antibodies. Nine of 20 patients were critically ill and were considered high-risk (HR). These patients showed significantly higher levels of transforming growth factor beta (TGF-ß) and myeloid-derived suppressor cells (MDSC), and lower levels of CD4+ T cells expressing LAG-3 compared to standard-risk (SR) patients. HR patients evidenced significantly higher anti-S1/RBD IgG antibody levels and an increased neutralizing activity. Importantly, a large proportion of S protein-specific antibodies were glycosylation-dependent and we identified a number of immunodominant linear epitopes within the S1 and N proteins. Findings derived from this study will not only help us to identify the most relevant component of the anti-SARS-CoV-2 humoral immune response but will also enable us to design more meaningful immunomonitoring methods for anti-COVID-19 vaccines.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Viral Proteins/immunology , Adaptive Immunity/immunology , Adult , Aged , COVID-19/virology , COVID-19 Vaccines/immunology , Coronavirus Nucleocapsid Proteins/genetics , Coronavirus Nucleocapsid Proteins/immunology , Coronavirus Nucleocapsid Proteins/metabolism , Female , Humans , Immunity, Humoral/immunology , Immunoglobulin G/genetics , Immunoglobulin G/immunology , Immunoglobulin G/metabolism , Male , Middle Aged , Mutation , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Viral Proteins/genetics , Viral Proteins/metabolism
3.
MAbs ; 14(1): 2002236, 2022.
Article in English | MEDLINE | ID: covidwho-1585298

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an evolving global public health crisis in need of therapeutic options. Passive immunization of monoclonal antibodies (mAbs) represents a promising therapeutic strategy capable of conferring immediate protection from SARS-CoV-2 infection. Herein, we describe the discovery and characterization of neutralizing SARS-CoV-2 IgG and VHH antibodies from four large-scale phage libraries. Each library was constructed synthetically with shuffled complementarity-determining region loops from natural llama and human antibody repertoires. While most candidates targeted the receptor-binding domain of the S1 subunit of SARS-CoV-2 spike protein, we also identified a neutralizing IgG candidate that binds a unique epitope on the N-terminal domain. A select number of antibodies retained binding to SARS-CoV-2 variants Alpha, Beta, Gamma, Kappa and Delta. Overall, our data show that synthetic phage libraries can rapidly yield SARS-CoV-2 S1 antibodies with therapeutically desirable features, including high affinity, unique binding sites, and potent neutralizing activity in vitro, and a capacity to limit disease in vivo.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Cell Surface Display Techniques , Immunoglobulin G/immunology , Peptide Library , SARS-CoV-2/immunology , Single-Domain Antibodies/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/genetics , Antibodies, Neutralizing/metabolism , Antibodies, Neutralizing/pharmacology , Antibodies, Viral/genetics , Antibodies, Viral/metabolism , Antibody Specificity , Binding Sites, Antibody , COVID-19/metabolism , COVID-19/prevention & control , COVID-19/virology , Chlorocebus aethiops , Disease Models, Animal , Epitopes , Female , Host-Pathogen Interactions , Immunoglobulin G/genetics , Immunoglobulin G/metabolism , Immunoglobulin G/pharmacology , Mesocricetus , SARS-CoV-2/pathogenicity , Single-Domain Antibodies/genetics , Single-Domain Antibodies/metabolism , Single-Domain Antibodies/pharmacology , Vero Cells
4.
Clin Transl Med ; 11(12): e668, 2021 12.
Article in English | MEDLINE | ID: covidwho-1568016

ABSTRACT

The level of postvaccine protection depends on two factors: antibodies and T-cell responses. While the first one is relatively easily measured, the measuring of the second one is a difficult problem. The recent studies indicate that the first one may be a good proxy for the protection, at least for SARS-CoV-2. The massive data currently gathered by both researcher and citizen scientists may be pivotal in confirming this observation, and the collective body of evidence is growing daily. This leads to an acceptance of IgG antibody levels as an accessible biomarker of individual's protection. With enormous and immediate need for assessing patient condition at the point of care, quantitative antibody analysis remains the most effective and efficient way to assess the protection against the disease. Let us not discount importance of reference points in the turmoil of current pandemics.


Subject(s)
Antibodies, Viral/chemistry , Antibodies/chemistry , Biomarkers/metabolism , COVID-19/blood , COVID-19/immunology , Antibody Specificity , Humans , Immune System , Immunity , Immunoglobulin G/metabolism , Intensive Care Units , Pandemics , Point-of-Care Systems , SARS-CoV-2 , Serologic Tests/methods , Serologic Tests/standards , Vaccines
5.
Nat Commun ; 12(1): 6250, 2021 10 29.
Article in English | MEDLINE | ID: covidwho-1493099

ABSTRACT

Understanding the trajectory, duration, and determinants of antibody responses after SARS-CoV-2 infection can inform subsequent protection and risk of reinfection, however large-scale representative studies are limited. Here we estimated antibody response after SARS-CoV-2 infection in the general population using representative data from 7,256 United Kingdom COVID-19 infection survey participants who had positive swab SARS-CoV-2 PCR tests from 26-April-2020 to 14-June-2021. A latent class model classified 24% of participants as 'non-responders' not developing anti-spike antibodies, who were older, had higher SARS-CoV-2 cycle threshold values during infection (i.e. lower viral burden), and less frequently reported any symptoms. Among those who seroconverted, using Bayesian linear mixed models, the estimated anti-spike IgG peak level was 7.3-fold higher than the level previously associated with 50% protection against reinfection, with higher peak levels in older participants and those of non-white ethnicity. The estimated anti-spike IgG half-life was 184 days, being longer in females and those of white ethnicity. We estimated antibody levels associated with protection against reinfection likely last 1.5-2 years on average, with levels associated with protection from severe infection present for several years. These estimates could inform planning for vaccination booster strategies.


Subject(s)
Antibodies, Viral/immunology , Antibody Formation/immunology , COVID-19/immunology , SARS-CoV-2/pathogenicity , Adult , Aged , Antibody Formation/physiology , Bayes Theorem , Female , Humans , Immunoglobulin G/metabolism , Male , Middle Aged , SARS-CoV-2/immunology
6.
Sci Rep ; 11(1): 20738, 2021 10 20.
Article in English | MEDLINE | ID: covidwho-1475484

ABSTRACT

Monoclonal antibodies that target SARS-CoV-2 with high affinity are valuable for a wide range of biomedical applications involving novel coronavirus disease (COVID-19) diagnosis, treatment, and prophylactic intervention. Strategies for the rapid and reliable isolation of these antibodies, especially potent neutralizing antibodies, are critical toward improved COVID-19 response and informed future response to emergent infectious diseases. In this study, single B cell screening was used to interrogate antibody repertoires of immunized mice and isolate antigen-specific IgG1+ memory B cells. Using these methods, high-affinity, potent neutralizing antibodies were identified that target the receptor-binding domain of SARS-CoV-2. Further engineering of the identified molecules to increase valency resulted in enhanced neutralizing activity. Mechanistic investigation revealed that these antibodies compete with ACE2 for binding to the receptor-binding domain of SARS-CoV-2. These antibodies may warrant further development for urgent COVID-19 applications. Overall, these results highlight the potential of single B cell screening for the rapid and reliable identification of high-affinity, potent neutralizing antibodies for infectious disease applications.


Subject(s)
Antibodies, Neutralizing/chemistry , B-Lymphocytes/virology , COVID-19/blood , COVID-19/immunology , SARS-CoV-2 , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antibodies, Monoclonal/immunology , Antibodies, Viral/immunology , B-Lymphocytes/immunology , Binding Sites/immunology , Biological Products , Female , HEK293 Cells , Humans , Immunoglobulin G/immunology , Immunoglobulin G/metabolism , Immunologic Memory , Mice , Mice, Inbred BALB C , Protein Binding , Spike Glycoprotein, Coronavirus , Vaccines
7.
Front Immunol ; 12: 748566, 2021.
Article in English | MEDLINE | ID: covidwho-1463474

ABSTRACT

Coronavirus disease 2019 (COVID-19) remains a major health challenge globally. Previous studies have suggested that changes in the glycosylation of IgG are closely associated with the severity of COVID-19. This study aimed to compare the profiles of IgG N-glycome between COVID-19 patients and healthy controls. A case-control study was conducted, in which 104 COVID-19 patients and 104 age- and sex-matched healthy individuals were recruited. Serum IgG N-glycome composition was analyzed by hydrophilic interaction liquid chromatography with the ultra-high-performance liquid chromatography (HILIC-UPLC) approach. COVID-19 patients have a decreased level of IgG fucosylation, which upregulates antibody-dependent cell cytotoxicity (ADCC) in acute immune responses. In severe cases, a low level of IgG sialylation contributes to the ADCC-regulated enhancement of inflammatory cytokines. The decreases in sialylation and galactosylation play a role in COVID-19 pathogenesis via the activation of the lectin-initiated alternative complement pathway. IgG N-glycosylation underlines the complex clinical phenotypes of SARS-CoV-2 infection.


Subject(s)
COVID-19/metabolism , Immunoglobulin G/metabolism , SARS-CoV-2/physiology , Adult , Antibody-Dependent Cell Cytotoxicity , Case-Control Studies , Chromatography, High Pressure Liquid , Complement Pathway, Mannose-Binding Lectin , Female , Glycosylation , Humans , Male , Middle Aged , Phenotype
8.
Front Immunol ; 12: 730766, 2021.
Article in English | MEDLINE | ID: covidwho-1463473

ABSTRACT

The SARS-CoV-2 pandemic has spread to all parts of the world and can cause life-threatening pneumonia and other severe disease manifestations known as COVID-19. This health crisis has resulted in a significant effort to stop the spread of this new coronavirus. However, while propagating itself in the human population, the virus accumulates mutations and generates new variants with increased fitness and the ability to escape the human immune response. Here we describe a color-based barcoded spike flow cytometric assay (BSFA) that is particularly useful to evaluate and directly compare the humoral immune response directed against either wild type (WT) or mutant spike (S) proteins or the receptor-binding domains (RBD) of SARS-CoV-2. This assay employs the human B lymphoma cell line Ramos, transfected for stable expression of WT or mutant S proteins or a chimeric RBD-CD8 fusion protein. We find that the alpha and beta mutants are more stably expressed than the WT S protein on the Ramos B cell surface and/or bind with higher affinity to the viral entry receptor ACE2. However, we find a reduce expression of the chimeric RBD-CD8 carrying the point mutation N501Y and E484K characteristic for the alpha and beta variant, respectively. The comparison of the humoral immune response of 12 vaccinated probands with 12 COVID-19 patients shows that after the boost, the S-specific IgG class immune response in the vaccinated group is similar to that of the patient group. However, in comparison to WT the specific IgG serum antibodies bind less well to the alpha variant and only poorly to the beta variant S protein. This is in line with the notion that the beta variant is an immune escape variant of SARS-CoV-2. The IgA class immune response was more variable than the IgG response and higher in the COVID-19 patients than in the vaccinated group. In summary, we think that our BSFA represents a useful tool to evaluate the humoral immunity against emerging variants of SARS-CoV-2 and to analyze new vaccination protocols against these variants.


Subject(s)
COVID-19/immunology , Cell Separation/methods , Flow Cytometry/methods , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Viral/metabolism , Antibody Formation , Female , Humans , Immunization, Secondary , Immunoglobulin A/metabolism , Immunoglobulin G/metabolism , Male , Middle Aged , Mutation/genetics , Spike Glycoprotein, Coronavirus/genetics , Vaccination
9.
Nat Immunol ; 22(11): 1452-1464, 2021 11.
Article in English | MEDLINE | ID: covidwho-1454797

ABSTRACT

There is limited understanding of the viral antibody fingerprint following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children. Herein, SARS-CoV-2 proteome-wide immunoprofiling of children with mild/moderate or severe coronavirus disease 2019 (COVID-19) versus multisystem inflammatory syndrome in children versus hospitalized control patients revealed differential cytokine responses, IgM/IgG/IgA epitope diversity, antibody binding and avidity. Apart from spike and nucleocapsid, IgG/IgA recognized epitopes in nonstructural protein (NSP) 2, NSP3, NSP12-NSP14 and open reading frame (ORF) 3a-ORF9. Peptides representing epitopes in NSP12, ORF3a and ORF8 demonstrated SARS-CoV-2 serodiagnosis. Antibody-binding kinetics with 24 SARS-CoV-2 proteins revealed antibody parameters that distinguish children with mild/moderate versus severe COVID-19 or multisystem inflammatory syndrome in children. Antibody avidity to prefusion spike correlated with decreased illness severity and served as a clinical disease indicator. The fusion peptide and heptad repeat 2 region induced SARS-CoV-2-neutralizing antibodies in rabbits. Thus, we identified SARS-CoV-2 antibody signatures in children associated with disease severity and delineate promising serodiagnostic and virus neutralization targets. These findings might guide the design of serodiagnostic assays, prognostic algorithms, therapeutics and vaccines in this important but understudied population.


Subject(s)
COVID-19 Serological Testing/methods , COVID-19/complications , COVID-19/immunology , SARS-CoV-2/immunology , Systemic Inflammatory Response Syndrome/immunology , Adolescent , Antibodies, Neutralizing/metabolism , Antibodies, Viral/metabolism , COVID-19/diagnosis , Child , Child, Preschool , Disease Progression , Epitopes/metabolism , Female , Hospitalization , Humans , Immunity, Humoral , Immunoglobulin A/metabolism , Immunoglobulin G/metabolism , Immunoglobulin M/metabolism , Male , Prognosis , Proteome , Severity of Illness Index , Systemic Inflammatory Response Syndrome/diagnosis
11.
J Exp Med ; 218(3)2021 03 01.
Article in English | MEDLINE | ID: covidwho-1406442

ABSTRACT

The identification of discrete subclasses within the immunoglobulin G (IgG) isotype by Grey and Kunkel (1964. J. Exp. Med.https://doi.org/10.1084/jem.120.2.253) provided the framework for our current understanding of differential IgG subclass activity in protective and self-reactive immune responses.


Subject(s)
Immunoglobulin G/metabolism , Antibody Formation/immunology , B-Lymphocytes/metabolism , COVID-19/immunology , Glycosylation , Humans , Multiple Myeloma/immunology , Multiple Myeloma/pathology
12.
Clin Immunol ; 231: 108850, 2021 10.
Article in English | MEDLINE | ID: covidwho-1401322

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has resulted in considerable morbidity and mortality in humans. Little is known regarding the development of immunological memory following SARS-CoV-2 infection or whether immunological memory can provide long-lasting protection against reinfection. Urgent need for vaccines is a considerable issue for all governments worldwide. METHODS: A total of 39 patients were recruited in this study. Tonsillar mononuclear cells (MNCs) were co-cultured in RPMI medium and stimulated with the full-length SARS-CoV-2 spike protein in the presence and absence of a CpG-DNA adjuvant. An enzyme-linked immunosorbent assay (ELISA) was utilised to measure the specific antibody response to the spike protein in the cell culture supernatants. RESULTS: The SARS-CoV-2 spike protein primed a potent memory B cell-mediated immune response in nasal-associated lymphoid tissue (NALT) from patients previously infected with the virus. Additionally, spike protein combined with the CpG-DNA adjuvant induced a significantly increased level of specific anti-spike protein IgG antibody compared with the spike protein alone (p < 0.0001, n = 24). We also showed a strong positive correlation between the specific anti-spike protein IgG antibody level in a serum samples and that produced by MNCs derived from the same COVID-19-recovered patients following stimulation (r = 0.76, p = 0.0002, n = 24). CONCLUSION: Individuals with serological evidence of previous SARS-CoV-2 exposure showed a significant anti-spike protein-specific memory humoral immune response to the viral spike protein upon stimulation. Additionally, our results demonstrated the functional response of NALT-derived MNCs to the viral spike protein. CpG-DNA adjuvant combined with spike protein induced significantly stronger humoral immune responses than the spike protein alone. These data indicate that the S protein antigen combined with CpG-DNA adjuvant could be used as a future vaccine candidate.


Subject(s)
COVID-19/immunology , COVID-19/virology , Immunologic Memory/physiology , Lymphoid Tissue/physiology , SARS-CoV-2/immunology , Antibodies, Viral/metabolism , B-Lymphocytes , Cells, Cultured , DNA , Enzyme-Linked Immunosorbent Assay , Humans , Immunity, Cellular , Immunity, Humoral , Immunoglobulin G/metabolism , Lymphoid Tissue/virology , Nose , Oligodeoxyribonucleotides , Spike Glycoprotein, Coronavirus/immunology
14.
Int J Mol Sci ; 22(6)2021 Mar 17.
Article in English | MEDLINE | ID: covidwho-1389395

ABSTRACT

As an essential modulator of IgG disposition, the neonatal Fc receptor (FcRn) governs the pharmacokinetics and functions many therapeutic modalities. In this review, we thoroughly reexamine the hitherto elucidated biological and thermodynamic properties of FcRn to provide context for our assessment of more recent advances, which covers antigen-binding fragment (Fab) determinants of FcRn affinity, transgenic preclinical models, and FcRn targeting as an immune-complex (IC)-clearing strategy. We further comment on therapeutic antibodies authorized for treating SARS-CoV-2 (bamlanivimab, casirivimab, and imdevimab) and evaluate their potential to saturate FcRn-mediated recycling. Finally, we discuss modeling and simulation studies that probe the quantitative relationship between in vivo IgG persistence and in vitro FcRn binding, emphasizing the importance of endosomal transit parameters.


Subject(s)
Histocompatibility Antigens Class I/chemistry , Histocompatibility Antigens Class I/metabolism , Receptors, Fc/chemistry , Receptors, Fc/metabolism , Animals , Antibodies, Monoclonal/metabolism , Antibodies, Monoclonal/pharmacokinetics , COVID-19/drug therapy , Histocompatibility Antigens Class I/immunology , Humans , Immunoglobulin G/immunology , Immunoglobulin G/metabolism , Receptors, Fc/immunology , Tissue Distribution/immunology
15.
Commun Biol ; 4(1): 225, 2021 02 12.
Article in English | MEDLINE | ID: covidwho-1387490

ABSTRACT

Serodiagnosis of SARS-CoV-2 infection is impeded by immunological cross-reactivity among the human coronaviruses (HCoVs): SARS-CoV-2, SARS-CoV-1, MERS-CoV, OC43, 229E, HKU1, and NL63. Here we report the identification of humoral immune responses to SARS-CoV-2 peptides that may enable discrimination between exposure to SARS-CoV-2 and other HCoVs. We used a high-density peptide microarray and plasma samples collected at two time points from 50 subjects with SARS-CoV-2 infection confirmed by qPCR, samples collected in 2004-2005 from 11 subjects with IgG antibodies to SARS-CoV-1, 11 subjects with IgG antibodies to other seasonal human coronaviruses (HCoV), and 10 healthy human subjects. Through statistical modeling with linear regression and multidimensional scaling we identified specific peptides that were reassembled to identify 29 linear SARS-CoV-2 epitopes that were immunoreactive with plasma from individuals who had asymptomatic, mild or severe SARS-CoV-2 infections. Larger studies will be required to determine whether these peptides may be useful in serodiagnostics.


Subject(s)
COVID-19/immunology , COVID-19/virology , Peptide Mapping , Peptides/immunology , SARS-CoV-2/physiology , Amino Acid Sequence , Animals , COVID-19/blood , Chiroptera , Epitopes/immunology , Humans , Immunoglobulin G/metabolism , Peptides/chemistry , Proteome/metabolism
16.
Sci Rep ; 11(1): 17325, 2021 08 30.
Article in English | MEDLINE | ID: covidwho-1379337

ABSTRACT

Two-dose messenger RNA vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly effective in preventing symptomatic COVID-19 infection. However, the durability of protection is not known, nor is the effectiveness against emerging viral variants. Additionally, vaccine responses may differ based on prior SARS-CoV-2 exposure history. To investigate protection against SARS-CoV-2 variants we measured binding and neutralizing antibody responses following both vaccine doses. We document significant declines in antibody levels three months post-vaccination, and reduced neutralization of emerging variants, highlighting the need to identify correlates of clinical protection to inform the timing of and indications for booster vaccination.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Neutralizing/analysis , COVID-19/prevention & control , SARS-CoV-2/immunology , Vaccines, Synthetic/administration & dosage , Adult , Antibodies, Neutralizing/metabolism , Antibodies, Viral/analysis , Antibodies, Viral/metabolism , COVID-19/immunology , COVID-19/metabolism , COVID-19 Nucleic Acid Testing , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Female , Humans , Immunoglobulin G/analysis , Immunoglobulin G/metabolism , Male , Middle Aged , Spike Glycoprotein, Coronavirus/metabolism , Time Factors , Vaccination , Vaccines, Synthetic/immunology , Young Adult
17.
EBioMedicine ; 71: 103561, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1372964

ABSTRACT

BACKGROUND: Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting risk of reinfection and durability of vaccine protection. METHODS: This is a prospective, monocentric, longitudinal, cohort clinical study. Healthcare workers (HCW) from Strasbourg University Hospital were enrolled between April 6th and May 7th, 2020 and followed up to 422 days. Serial serum samples were tested for antibodies against the Receptor Binding Domain (RBD) of the spike protein and nucleocapsid protein (N) to characterize the kinetics of SARS-CoV-2 antibodies and the incidence of reinfection. Live-neutralization assays were performed for a subset of samples before and after vaccination to analyze sensitivity to SARS-CoV-2 variants. FINDINGS: A total of 4290 samples from 393 convalescent COVID-19 and 916 COVID-19 negative individuals were analyzed. In convalescent individuals, SARS-CoV-2 antibodies followed a triphasic kinetic model with half-lives at month (M) 11-13 of 283 days (95% CI 231-349) for anti-N and 725 days (95% CI 623-921) for anti-RBD IgG, which stabilized at a median of 1.54 log BAU/mL (95% CI 1.42-1.67). The incidence of SARS-CoV-2 infections was 12.22 and 0.40 per 100 person-years in COVID-19-negative and COVID-19-positive HCW, respectively, indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7%. Live-virus neutralization assay revealed that after one year, variants D614G and B.1.1.7, but less so B.1.351, were sensitive to anti-RBD antibodies at 1.4 log BAU/mL, while IgG ≥ 2.0 log BAU/mL strongly neutralized all three variants. These latter anti-RBD IgG titers were reached by all vaccinated HCW regardless of pre-vaccination IgG levels and type of vaccine. INTERPRETATION: Our study demonstrates a long-term persistence of anti-RBD antibodies that may reduce risk of reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against variants. FUN1DING: None.


Subject(s)
COVID-19/pathology , Immunity, Humoral , Reinfection/pathology , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Antibodies, Viral/metabolism , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Coronavirus Nucleocapsid Proteins/immunology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin G/metabolism , Kinetics , Longitudinal Studies , Male , Middle Aged , Phosphoproteins/immunology , Prospective Studies , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/immunology , Time Factors
18.
Clin Chem Lab Med ; 59(11): 1878-1884, 2021 10 26.
Article in English | MEDLINE | ID: covidwho-1341521

ABSTRACT

OBJECTIVES: Numerous analytical systems, rapidly made available on the market throughout the SARS-CoV-2 pandemic, aim to detect COVID-19, and to continuously update and improve the same systems. Medical laboratory professionals have also developed in-house analytical procedures in order to satisfy the enormous volume of requests for tests. These developments have highlighted the need control the analytical procedures used in order to guarantee patient safety. The External Quality Assessment (EQA) Scheme, an important quality assurance tool, aims to guarantee high standard performance for laboratory and analytical procedures. The aim of the present study was to report on the results collected in an experimental EQA scheme for the serological diagnosis of SARS-CoV-2. METHODS: All qualitative results collected in the different EQA surveys were summarized in order to identify the percentage of laboratory results in relation to typology of antibodies, results and samples. RESULTS: A total of 4,867 data sets were collected. The analysis of EQA data made, demonstrates a better agreement among laboratories results for total Ig than single immunoglobulins (IgG, IgM, IgA) in the case samples positive for SARS-CoV-2, and a wide divergence between IgM results for positive samples (only 34.9% were correct). Results for negative controls and specificity controls demonstrated a better overall agreement than results for positive samples. CONCLUSIONS: Working in collaboration with the IVD manufacturers, laboratory professionals must strive to achieve harmonization of results, and to develop well-defined protocols complying with the ISO 15189 requirements.


Subject(s)
Antibodies, Viral/immunology , COVID-19/diagnosis , SARS-CoV-2/immunology , Serologic Tests/methods , Antibodies, Viral/blood , COVID-19/immunology , Humans , Immunoglobulin A/blood , Immunoglobulin A/metabolism , Immunoglobulin G/blood , Immunoglobulin G/metabolism , Immunoglobulin M/blood , Immunoglobulin M/metabolism , Pilot Projects , Quality Assurance, Health Care , Retrospective Studies , Sensitivity and Specificity , Severity of Illness Index
19.
Sci Rep ; 11(1): 14390, 2021 07 13.
Article in English | MEDLINE | ID: covidwho-1309469

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic affected people at all ages. Whereas pregnant women seemed to have a worse course of disease than age-matched non-pregnant women, the risk of feto-placental infection is low. Using a cohort of 66 COVID-19-positive women in late pregnancy, we correlated clinical parameters with disease severity, placental histopathology, and the expression of viral entry and Interferon-induced transmembrane (IFITM) antiviral transcripts. All newborns were negative for SARS-CoV-2. None of the demographic parameters or placental histopathological characteristics were associated with disease severity. The fetal-maternal transfer ratio for IgG against the N or S viral proteins was commonly less than one, as recently reported. We found that the expression level of placental ACE2, but not TMPRSS2 or Furin, was higher in women with severe COVID-19. Placental expression of IFITM1 and IFITM3, which have been implicated in antiviral response, was higher in participants with severe disease. We also showed that IFITM3 protein expression, which localized to early and late endosomes, was enhanced in severe COVID-19. Our data suggest an association between disease severity and placental SARS-CoV-2 processing and antiviral pathways, implying a role for these proteins in placental response to SARS-CoV-2.


Subject(s)
COVID-19/metabolism , Placenta/metabolism , SARS-CoV-2/pathogenicity , Adult , Angiotensin-Converting Enzyme 2/metabolism , Female , Furin/metabolism , Humans , Immunoglobulin G/metabolism , Infectious Disease Transmission, Vertical , Male , Nucleocapsid Proteins/metabolism , Pregnancy , Pregnancy Complications, Infectious/metabolism , Pregnancy Complications, Infectious/virology , Serine Endopeptidases/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Young Adult
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